Objective To evaluate the in vitro anti-hypertrophic effect of total Glycosides of Ranunculus Japonius （TGRJ）. Methods Neonatal rat cardiomyocytes were cultured and hypertrophy was induced by adminis- trating isopr...Objective To evaluate the in vitro anti-hypertrophic effect of total Glycosides of Ranunculus Japonius （TGRJ）. Methods Neonatal rat cardiomyocytes were cultured and hypertrophy was induced by adminis- trating isoproterenol （ISO, 10 gmol/L） or angiotensin Ⅱ （AngⅡ, 1 gmol/L） for 48 hours. In the treatment groups, cells were pretreated with TGRJ （0.3 g/L） for 30 minutes prior to hypertrophic stimuli. The anti-hypertrophic effects of TGRJ were examined by measuring cell size, total protein content, and protein synthesis. Intracellular free Ca2＋ concentration （[Ca2＋]i） was evaluated using fluorescence dye Fura-2/AM. Sacroplasmic/endoplasmic reticulum Ca2＋ ATPase 2a （SERCA2a）, atrial natriuretic peptide （ANP）, B-type natriuretic peptide （BNP）, and beta-myosin heavy chain （β-MHC） protein expression levels were measured by Western blotting. SERCA2a activity was assayed by p-nitrophenal phosphate disodium salt hexahydrate method. Results Increased cell size, total protein content, and protein synthesis following ISO or Ang II stimulation were significantly inhibited by pretreatment with TGRJ （all P〈0.05）. This anti-hypertrophic effect of TGRJ was confirmed by its suppressing effect on elevated expression of the three hypertrophic related genetic markers, ANP, BNP, and ^-MHC. In addition, TGRJ inhibited ISO or Ang Ⅱ induced up-regulation of [Ca2＋] under chronic but not acute conditions. And ISO or Ang Ⅱ induced down-regulation of SERCA2a expression and activity was also effectively rectified byTGRJ pretreatment. Conclusions The results of present study suggested that TGRJ could prevent ISO or Ang Ⅱ induced cardiac hypertrophy through improving chronic [Ca2＋]i disorder, might via normalizing SERCA2a expression and activity.展开更多
Objective To investigate the effect and significance of cardiomyocyte apoptosis and cardio-myocyte proliferation on cardiac hypertrophy by observing the dynamic changes of them during the development ofcardiac hypertr...Objective To investigate the effect and significance of cardiomyocyte apoptosis and cardio-myocyte proliferation on cardiac hypertrophy by observing the dynamic changes of them during the development ofcardiac hypertrophy in spontaneously hypertensive rats (SHR). Methods Hearts were excised from SHR andWistar-Kyoto rats(WKY) at different ages. Cardiac hypertrophic index (CHI) was calculated as the radio of heartweight to body weight; Cardiomyocyte apoptosis was identified by in situ TUT-mediated dUTP nick end labeling( TUNEL) ; Localization and expression of proliferating cell nuclear antigen (PCNA) were examined by immunohis-tochemistry. Results Compared with age-matched WKY, CHI in SHR was significantly increased at 12 weeksold and 24 weeks old (3.604 ±0.089 vs 2. 997 ±0.166, P <0. 01; 4. 156 ±0.385 vs 3. 119 ±0.208, P <0. 01) ,and CHI in SHR was increased little by little with the age increasing and attained platform since 20 weeks old. Incontrast with age-matched WKY, cardiomyocyte apoptotic index (APOI) in SHR at 12 weeks was not increased sig-nificantly (4. 248 ± 1. 592 vs 3. 678 ± 0. 856, P >0. 05) , but decreased markedly when their age were 24 weeks(3. 207 ± 1. 794 vs 5. 494 ± 1. 372, P<0.05); APOI in SHR at 12 weeks old, 16 weeks old, 20 weeks old and 24weeks old were 4. 248 ±1. 592, 5.707 ±1. 322, 7. 436 ± 1. 128, 3. 207 ± 1. 794, respectively. On the other hand,APOI in SHR from 12 weeks old to 20 weeks old increased gradually, and attained peak at 20 weeks old, but de-creased markedly after 20 weeks old (P <0. 01). Compared with age-matched WKY, the rate of cardiomyocyte PC-NA positive labeling (PCNAR) in SHR at 12 weeks old and 24 weeks old didn’ t have obvious difference. Conclu-sion Imbalance of cardiomyocyte apoptosis and cardiomyocyte proliferation existed during the development of car-diac hypertrophy in spontaneously hypertensive rats.展开更多
OBJECTIVE: To explore the pathogenic changes of myocardial apoptosis in heart hypertrophy during hypertension and evaluate the anti-apoptosis effect of Valsartan. METHODS: Thirty spontaneously hypertensive rats (SHRs)...OBJECTIVE: To explore the pathogenic changes of myocardial apoptosis in heart hypertrophy during hypertension and evaluate the anti-apoptosis effect of Valsartan. METHODS: Thirty spontaneously hypertensive rats (SHRs) were divided into two groups: 15 treated with Valsartan (20 mg x kg(-1) x d(-1)) (SHR + Valsartan group), the others with placebo (SHR + placebo group), with 15 normal Wistar rats as control. Systolic blood pressure was measured by the tail-cuff method. The observation period was from 8 to 16 weeks of age. Cardiac apoptosis was evaluated by a Terminal Deoxynucleotidyl Transferase-Mediated dUTP-biotin Nick End Labeling (TUNEL) assay. RESULTS: Mean blood pressure values were 127 +/- 2 mm Hg in controls, 163 +/- 6 mm Hg in the SHR + Valsartan group and 193 +/- 7 mm Hg in the SHR + placebo group at 16 weeks of age, whereas the blood pressure in 8-week-old SHR and Wistar rats were 175 +/- 3 mm Hg and 125 +/- 5 mm Hg, respectively. The ratio of the heart weight over body weight declined in Wistar (3.07 +/- 0.03 mg/g) and SHR + Valsartan groups (3.22 +/- 0.19 mg/g) compared with the SHR + placebo group (4.02 +/- 0.31 mg/g) (P展开更多
文摘Objective To evaluate the in vitro anti-hypertrophic effect of total Glycosides of Ranunculus Japonius （TGRJ）. Methods Neonatal rat cardiomyocytes were cultured and hypertrophy was induced by adminis- trating isoproterenol （ISO, 10 gmol/L） or angiotensin Ⅱ （AngⅡ, 1 gmol/L） for 48 hours. In the treatment groups, cells were pretreated with TGRJ （0.3 g/L） for 30 minutes prior to hypertrophic stimuli. The anti-hypertrophic effects of TGRJ were examined by measuring cell size, total protein content, and protein synthesis. Intracellular free Ca2＋ concentration （[Ca2＋]i） was evaluated using fluorescence dye Fura-2/AM. Sacroplasmic/endoplasmic reticulum Ca2＋ ATPase 2a （SERCA2a）, atrial natriuretic peptide （ANP）, B-type natriuretic peptide （BNP）, and beta-myosin heavy chain （β-MHC） protein expression levels were measured by Western blotting. SERCA2a activity was assayed by p-nitrophenal phosphate disodium salt hexahydrate method. Results Increased cell size, total protein content, and protein synthesis following ISO or Ang II stimulation were significantly inhibited by pretreatment with TGRJ （all P〈0.05）. This anti-hypertrophic effect of TGRJ was confirmed by its suppressing effect on elevated expression of the three hypertrophic related genetic markers, ANP, BNP, and ^-MHC. In addition, TGRJ inhibited ISO or Ang Ⅱ induced up-regulation of [Ca2＋] under chronic but not acute conditions. And ISO or Ang Ⅱ induced down-regulation of SERCA2a expression and activity was also effectively rectified byTGRJ pretreatment. Conclusions The results of present study suggested that TGRJ could prevent ISO or Ang Ⅱ induced cardiac hypertrophy through improving chronic [Ca2＋]i disorder, might via normalizing SERCA2a expression and activity.
基金Supported by Shanghai Science and Technology Committee (024119018)
文摘Objective To investigate the effect and significance of cardiomyocyte apoptosis and cardio-myocyte proliferation on cardiac hypertrophy by observing the dynamic changes of them during the development ofcardiac hypertrophy in spontaneously hypertensive rats (SHR). Methods Hearts were excised from SHR andWistar-Kyoto rats(WKY) at different ages. Cardiac hypertrophic index (CHI) was calculated as the radio of heartweight to body weight; Cardiomyocyte apoptosis was identified by in situ TUT-mediated dUTP nick end labeling( TUNEL) ; Localization and expression of proliferating cell nuclear antigen (PCNA) were examined by immunohis-tochemistry. Results Compared with age-matched WKY, CHI in SHR was significantly increased at 12 weeksold and 24 weeks old (3.604 ±0.089 vs 2. 997 ±0.166, P <0. 01; 4. 156 ±0.385 vs 3. 119 ±0.208, P <0. 01) ,and CHI in SHR was increased little by little with the age increasing and attained platform since 20 weeks old. Incontrast with age-matched WKY, cardiomyocyte apoptotic index (APOI) in SHR at 12 weeks was not increased sig-nificantly (4. 248 ± 1. 592 vs 3. 678 ± 0. 856, P >0. 05) , but decreased markedly when their age were 24 weeks(3. 207 ± 1. 794 vs 5. 494 ± 1. 372, P<0.05); APOI in SHR at 12 weeks old, 16 weeks old, 20 weeks old and 24weeks old were 4. 248 ±1. 592, 5.707 ±1. 322, 7. 436 ± 1. 128, 3. 207 ± 1. 794, respectively. On the other hand,APOI in SHR from 12 weeks old to 20 weeks old increased gradually, and attained peak at 20 weeks old, but de-creased markedly after 20 weeks old (P <0. 01). Compared with age-matched WKY, the rate of cardiomyocyte PC-NA positive labeling (PCNAR) in SHR at 12 weeks old and 24 weeks old didn’ t have obvious difference. Conclu-sion Imbalance of cardiomyocyte apoptosis and cardiomyocyte proliferation existed during the development of car-diac hypertrophy in spontaneously hypertensive rats.
文摘OBJECTIVE: To explore the pathogenic changes of myocardial apoptosis in heart hypertrophy during hypertension and evaluate the anti-apoptosis effect of Valsartan. METHODS: Thirty spontaneously hypertensive rats (SHRs) were divided into two groups: 15 treated with Valsartan (20 mg x kg(-1) x d(-1)) (SHR + Valsartan group), the others with placebo (SHR + placebo group), with 15 normal Wistar rats as control. Systolic blood pressure was measured by the tail-cuff method. The observation period was from 8 to 16 weeks of age. Cardiac apoptosis was evaluated by a Terminal Deoxynucleotidyl Transferase-Mediated dUTP-biotin Nick End Labeling (TUNEL) assay. RESULTS: Mean blood pressure values were 127 +/- 2 mm Hg in controls, 163 +/- 6 mm Hg in the SHR + Valsartan group and 193 +/- 7 mm Hg in the SHR + placebo group at 16 weeks of age, whereas the blood pressure in 8-week-old SHR and Wistar rats were 175 +/- 3 mm Hg and 125 +/- 5 mm Hg, respectively. The ratio of the heart weight over body weight declined in Wistar (3.07 +/- 0.03 mg/g) and SHR + Valsartan groups (3.22 +/- 0.19 mg/g) compared with the SHR + placebo group (4.02 +/- 0.31 mg/g) (P
